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  • American Association for Cancer Research (AACR)  (3)
  • 1
    Online Resource
    Online Resource
    Abstract 3149: OncoPredictor: A systematic approach for predicting responsive cancer populations from large scale cell line screening
    American Association for Cancer Research (AACR) ; 2011
    In:  Cancer Research Vol. 71, No. 8_Supplement ( 2011-04-15), p. 3149-3149
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 71, No. 8_Supplement ( 2011-04-15), p. 3149-3149
    Abstract: Investigational new drugs for cancer must demonstrate convincing preclinical efficacy and a compelling strategy to translate preclinical observations to the clinical setting. Personalized medicine approaches are gaining wider acceptance, and large scale cell line databases have demonstrated utility in identifying biomarkers of drug response that can inform clinical development strategies. However, the lack of an integrated platform to translate preclinical biomarker profiles to clinical populations limits the power of this approach. To solve this problem we developed, first, a cell line screening and genomic analysis pipeline that associates drug response across 200+ cell lines with mutation, DNA copy number, and gene expression biomarkers; and second, a parallel database of biomarker frequencies in clinical tumor samples, compiled from all available published genomic data. In the present study, we tested 8 targeted anti-cancer agents and identified cell line biomarkers representing each of the genomic data types – mutation, DNA amplification, and gene over-expression – and then assessed the distribution of these biomarkers across tumor samples. In each case the tumor populations predicted to be responsive by this unsupervised approach were validated by results from clinical trials. We also present an example of biomarker results leading to potential new indications for an approved drug. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3149. doi:10.1158/1538-7445.AM2011-3149
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2011-3149
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2011
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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  • 2
    Online Resource
    Online Resource
    Implication of ZNF217 in Accelerating Tumor Development and Therapeutically Targeting ZNF217-Induced PI3K–AKT Signaling for the Treatment of Metastatic Osteosarcoma
    American Association for Cancer Research (AACR) ; 2020
    In:  Molecular Cancer Therapeutics Vol. 19, No. 12 ( 2020-12-01), p. 2528-2541
    Details
    In: Molecular Cancer Therapeutics, American Association for Cancer Research (AACR), Vol. 19, No. 12 ( 2020-12-01), p. 2528-2541
    Abstract: We previously identified ZNF217 as an oncogenic driver of a subset of osteosarcomas using the Sleeping Beauty (SB) transposon system. Here, we followed up by investigating the genetic role of ZNF217 in osteosarcoma initiation and progression through the establishment of a novel genetically engineered mouse model, in vitro assays, orthotopic mouse studies, and paired these findings with preclinical studies using a small-molecule inhibitor. Throughout, we demonstrate that ZNF217 is coupled to numerous facets of osteosarcoma transformation, including proliferation, cell motility, and anchorage independent growth, and ultimately promoting osteosarcoma growth, progression, and metastasis in part through positive modulation of PI3K–AKT survival signaling. Pharmacologic blockade of AKT signaling with nucleoside analogue triciribine in ZNF217+ orthotopically injected osteosarcoma cell lines reduced tumor growth and metastasis. Our data demonstrate that triciribine treatment may be a relevant and efficacious therapeutic strategy for patients with osteosarcoma with ZNF217+ and p-AKT rich tumors. With the recent revitalization of triciribine for clinical studies in other solid cancers, our study provides a rationale for further evaluation preclinically with the purpose of clinical evaluation in patients with incurable, ZNF217+ osteosarcoma.
    Type of Medium: Online Resource
    ISSN: 1535-7163 , 1538-8514
    URL: Article
    DOI: 10.1158/1535-7163.MCT-20-0369
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2020
    detail.hit.zdb_id: 2062135-8
    SSG: 12
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  • 3
    Online Resource
    Online Resource
    Multiphoton Tomographic Imaging: A Potential Optical Biopsy Tool for Detecting Gastrointestinal Inflammation and Neoplasia
    American Association for Cancer Research (AACR) ; 2012
    In:  Cancer Prevention Research Vol. 5, No. 11 ( 2012-11-01), p. 1280-1290
    Details
    In: Cancer Prevention Research, American Association for Cancer Research (AACR), Vol. 5, No. 11 ( 2012-11-01), p. 1280-1290
    Abstract: Endoscopy is widely used to detect and remove premalignant lesions with the goal of preventing gastrointestinal (GI) cancers. Because current endoscopes do not provide cellular resolution, all suspicious lesions are biopsied and subjected to histologic evaluation. Technologies that facilitate directed biopsies should decrease both procedure-related morbidity and cost. Here we explore the use of multiphoton microscopy (MPM), an optical biopsy tool that relies on intrinsic tissue emissions, to evaluate pathology in both experimental and human GI specimens, using hematoxylin and eosin (H & E)-stained sections from these tissues for comparison. After evaluating the entire normal mouse GI tract, MPM was used to investigate disease progression in mouse models of colitis and colorectal carcinogenesis. MPM provided sufficient histologic detail to identify all relevant substructures in ex vivo normal GI tissue, visualize both acute and resolving stages of colitis, and show the progression of colorectal carcinogenesis. Next, ex vivo specimens from human subjects with celiac sprue, inflammatory bowel disease, and colorectal neoplasia were imaged by MPM. Finally, colonic mucosa in live anesthetized rats was imaged in vivo using a flexible endoscope prototype. In both animal models and human specimens, MPM images showed a striking similarity to the results of H & E staining, as shown by the 100% concordance achieved by the study pathologists' diagnoses. In summary, MPM is a promising technique that accurately visualizes histology in fresh, unstained tissues. Our findings support the continued development of MPM as a technology to enhance the early detection of GI pathologies including premalignant lesions. Cancer Prev Res; 5(11); 1280–90. ©2012 AACR.
    Type of Medium: Online Resource
    ISSN: 1940-6207 , 1940-6215
    URL: Article
    DOI: 10.1158/1940-6207.CAPR-12-0132
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2012
    detail.hit.zdb_id: 2422346-3
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